Many halogenated compounds including chemical warfare agents such as HD can be decontaminated into a less toxic form via oxidation reactions through the use of, for example, aqueous bleach or via substitution reactions through the use of, for example, aqueous alkali, organic alkali, basic hydrogen peroxide, or monoethanolamine. Typically, such decontamination reactants exhibit desirable rapid reaction rates and broad range reactivity. However, they often are limited in terms of material incompatibility. In addition, they usually require large quantities to achieve acceptable results, which can impose serious logistical burdens.
Oxidizing reactants offer a particularly broad-spectrum approach to decontamination. However, oxidizing reactants exhibit unpredictable chemical stability. Moreover, the logistics needed to handle and administer such oxidizing reactants are often problematic due to the typically unfavorable stoichiometry. Some oxidation/substitution reactions have also been shown to be effective against biological agents; there are others that may be effective but remain untested.
Hydrolysis reactions can be effective in decontamination, and offer their own unique advantages including substantially more favorable stoichiometry (one or two water molecules react with one agent molecule of about 10 times greater mass) and the nearly widespread availability of water. Hydrolysis can be used to decontaminate or break down HD also known as mustard gas (sulfur mustard, 2,2′-dichlorodiethyl sulfide) to yield thiodiglycol (TDG). The difference in toxicity between HD and TDG is a factor of 4,200 to 5,700 (the oral LD50 of HD is 0.7 mg/kg whereas that of TDG is 3000-4000 mg/kg). This large reduction in toxicity offers the potential to seriously reduce the damage caused by HD if it can be decontaminated in a rapid manner. The hydrolysis reaction of HD is shown in Scheme 1 below.

For purposes of decontamination, the HD hydrolysis reaction offers the important advantage of yielding a product (thiodiglycol, 2,2′-thiodiethanol) that is water soluble, biodegradable, and of very low toxicity (approximately 5,000 times less toxid than HD). However, the direct reaction between HD and water is too slow to use for decontamination under ambient conditions.
The rates of hydrolysis reactions are generally low in comparison to oxidation reactions. Such reactions including HD hydrolysis reactions can be accelerated significantly with the use of hydrolysis-enhancing agents such as catalysts and surfactants. In particular, such catalysts including enzymes can dramatically increase the rate of reaction by lowering the activation energy of the reaction pathway. However, catalysts exhibit a relatively narrow specificity of activity, where significant activity differences can be observed between even two stereoisomers of the same compound.
Decontamination reactions using catalytic enzymes are well characterized. In the decontamination of G-type organophosphate chemical nerve agents, they have been used for a range of G-type substrates. For example, organophosphate hydrolase (OPH) enzymes have been shown to catalyze and enhance the hydrolysis of the P-S bond in V-type phosphonothiolate agents.
Hydrolytic dehalogenase enzymes have been found to possess dehalogenase activity against HD upon dissolving the HD compound in alcohol, and then adding the resulting mixture to the enzymes in an aqueous reaction matrix. In the absence of alcohol, neat HD is substantially insoluble in water and the HD molecules would be inaccessible to the enzymes. In this manner, the use of surfactants or compounds that increase the water solubility or dispersion of HD in the aqueous matrix can be used to further enhance and accelerate the rate of reaction. Thus, the search and selection of suitable hydrolysis enhancing agents including surfactants, phase transfers catalysts, enzymes and the like, would greatly aid the rapid decontamination of water insoluble chemical warfare agents such as HD. The reactivity of other halogenated compounds could be similarly accelerated.
Such search is tedious and time-consuming. The determination of the hydrolysis rate of HD and other halogenated compounds is technically problematic, due largely in part to the heterogenous nature of the reaction between water and such compounds. The aqueous-insoluble HD undergoes an interfacial reaction with the surrounding water molecules. The rate of the mass-transfer limited reaction is difficult to measure in a reproducible manner because small and essentially random differences in the physical conformation of the HD droplets in the reaction can cause large differences in the overall hydrolysis rate.
There are several means available to measure or estimate the HD hydrolysis rate. For instance, the rate can be measured using a chloride electrode to monitor the rate of chloride release as the HD undergoes hydrolysis. Alternatively, the biphasic reaction can be extracted with an organic solvent from which the residual HD can be analyzed by chromatography. Prior to the availability of modern chromatographic instruments, the overall time of reaction was measured by the visual disappearance of the organic HD layer from the reaction. Such approaches have inherently large variability caused by the variations in the size and shape of the hydrophobic mustard droplets in the reaction. Even under conditions of well controlled agitation, the physical properties of HD cause it to disperse in a highly variable manner. In addition, these assays are relatively labor intensive and time consuming, and frequently require the use of expensive instruments. Particularly within the confines of a high containment laboratory, these limitations are very significant.
For this reason, it would be useful to rapidly and inexpensively screen for potentially useful compounds that enhance the hydrolysis of chemical warfare agents such as HD. Such compounds would be selected based on their capacity to increase the rate of reaction and/or enhance solubility and contact of chemical warfare agents in an aqueous matrix. There is a need to develop a practical means of accurately testing to visually compare hydrolysis rates of various compounds in the presence of the chemical warfare agent in a consistent, reliable manner.